The disproportionately higher smoking prevalence and greater difficulty quitting among individuals prone to depression suggests that smoking may serve an important function in this population. Emerging data point to diminished reward processing and dysregulated positive affect as two processes potentially ameliorated by smoking in depression-prone (DP+) smokers. Individuals prone to depression have fewer alternative reinforcers, derive less reward from natural reinforcers in their environment, and have diminished positive affect. Smoking is a reinforcing behavior, it can substitute for limited alternative reinforcers, enhance reward from those reinforcers that are available, and increase positive affect. According to Behavioral Economic Theory, the choice to smoke depends on the presence of alternative reinforcers and that the reinforcing value of smoking can be enhanced, or reduced, based on the alternatives. Compared to smokers not prone to depression (DP-), we hypothesize that DP+ smokers (1) have a heightened relative reinforcing value of smoking in the context of fewer alternative reinforcers, and (2) experience greater changes in positive affect and subjective reward from available alternative reinforcers when smoking as usual compared to smoking abstinence. These hypotheses will be tested in smokers (n=100), ages 18-65 years old using a within-subjects design with between-group comparisons (DP+ vs. DP- smokers). DP+ smokers are defined as smokers with a past history of major depression on the Inventory to Diagnose Depression-Lifetime and a score >16 on the Center for Epidemiological Studies Depression scale. The relative reinforcing value of smoking will be measured with a validated smoking choice paradigm. Changes in positive affect and subjective reward (pleasure) derived from alternative reinforcers in the natural environment will be prospectively measured via Experience Sampling across a 3-day smoking ad-lib phase and a 3-day smoking abstinence phase (order counterbalanced). Investigation of the role of smoking in reward processing and positive affect regulation among DP+ smokers may illuminate unique smoking mechanisms and novel smoking cessation treatment targets to inform more effective smoking cessation interventions for DP+ smokers. PUBLIC HEALTH RELEVANCE: The over-representation of smoking and greater difficulty quitting among individuals prone to depression suggests that smoking serves an important function in this population. Investigation of the role of smoking in reward and positive affect regulation may illuminate novel smoking cessation treatment targets and inform more effective treatment for these smokers.